The applicant will study the total synthesis of several potent, naturally occurring antifungal agents including (1) the nikkomycins and neopolyoxins which are nucleoside dipeptide chitin synthetase inhibitors produced by Streptomyces tendae or cacaoi var asoensis; (2) jaspamide which is a marine peptide polyketide macrocycle produced by a sponge of the genus Jaspis; (3) papulacandin A which is a 1,3-beta-D-glucan synthase inhibitor elaborated by Papularia sphaerosperma; (4) trichoviridin which is an epoxy isonitrile derivative produced by a Trichoderma species. It is the intention of this study to clarify the mode of action of these active compounds and thereby design more active analogs and to develop novel organic transformations of general synthetic importance. Specifically the applicant shall seek to develop (1) the use of isoxazoline intermediates in stereospecific gamma- hydroxy-alpha- amino acid construction; (2) the homologation of ribose aldehydes in the stereochemically controlled synthesis of nucleoside amino acids; (3) the elaboration of macrocyclic seco acids units via the diastereoselective alkylation of N-propanoyl alanine trianions; (4) macrocyclization via N-acyl-2-azetidinones and transacylation; (5) the regioselective manipulation of D-lactose using 4-azido-2,2- dimethylbutanoyl chloride and aryl titanium chelates (6) the construction of alpha,beta-epoxy isonitriles via the corresponding isocyanates or isothiocyanates and deoxygenation or desulfurization or via chromium carbene chemistry.